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Little discrepancy of one-stage and chromogenic assays in a large international cohort of patients with non-severe hemophilia A and B (DYNAMO study)

1Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands, Amsterdam, Noord-Holland, Netherlands, 2Department of Pediatric Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands, Amsterdam, Noord-Holland, Netherlands, 3Department of Haematology, University Hospital Southampton, Southampton, United Kingdom, Southampton, England, United Kingdom, 4Department of Pediatric Hemato-Oncology, Radboud University Medical Center, Nijmegen, the Netherlands, Nijmegen, Gelderland, Netherlands, 5Department of Pediatric Hematology, Sophia Children’s Hospital, Erasmus University Medical Center, Erasmus University Rotterdam, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands, 6Medical School of Cardiff University, Cardiff, Wales, United Kingdom, 7Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Leiden, Zuid-Holland, Netherlands, 8University Department of Haematology, Manchester Royal Infirmary, Manchester, England, United Kingdom, 9Adult Bleeding Disorders Program of BC - Adult Division St. Paul's Hospital, Vancouver, British Columbia, Canada, Vancouver, British Columbia, Canada, 10Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 11Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, The Netherlands, Nijmegen, Gelderland, Netherlands, 12 Medical University of Vienna, Austria, Vienna, Wien, Austria, 13Department of Hematology, Máxima Medical Center, Eindhoven, Netherlands; Radboud university medical center, Hemophilia Treatment Center, Nijmegen – Eindhoven – Maastricht, Netherlands, Eindhoven, Noord-Brabant, Netherlands, 14Oxford University Hospitals NHS Foundation Trust, Oxford, England, United Kingdom, 15Department of Pediatric Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands, Amsterdam, Noord-Holland, Netherlands, 16Amsterdam University Medical Centers, Amsterdam, the Netherlands, Amsterdam, Noord-Holland, Netherlands

Abstract Number: OC 63.4

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Measurements of coagulation factor activity are essential for hemophilia management and are generally performed with the one-stage or chromogenic assay. Currently it is suggested that around one-third of patients with non-severe hemophilia A have assay discrepancy. These data are limited for non-severe hemophilia B. Knowledge on the extent of assay discrepancy in perspective of previous literature may facilitate further interpretation of this phenomenon.

Aims: To investigate the extent of assay discrepancy in moderate and mild hemophilia A and B.

Methods: Patients with non-severe hemophilia A and B were included from the multicenter international DYNAMO study. Central measurements of FVIII and FIX activity levels were performed by the one-stage (Actin FS reagents) and chromogenic assay (FVIII Siemens, FIX Rossix). Assay discrepancy was defined as a ratio >2.0 or < 0.5 between the assay results according to the SSC ISTH. Ethics approval and written consent was obtained (ClinicalTrials.gov: NCT03623295).

Results: A total of 221 patients were included of whom 4 patients (2%) showed assay discrepancy. This corresponded to 2/175 hemophilia A patients and 2/46 hemophilia B patients. Another 4 patients did not meet the criteria but exhibited a potential clinically relevant absolute difference >10 IU/dL between the assay results. The median difference between the assays was generally low with 1.1 IU/dL (IQR 0.5-2.1) for the total cohort, 1.0 IU/dL (IQR 0.4-1.9) in case of higher one-stage results and 1.3 IU/dL (IQR 0.7-2.4) in case of higher chromogenic results (Figure 1). Thirteen patients in this cohort had a F8/F9 mutation associated with assay discrepancy in at least 3 patients in previous literature. Most of these patients (92%) had no discrepant results in our study.

Conclusion(s): Little assay discrepancy was observed, even in those persons with mutations previously associated with discrepancy. This suggests that the previously reported discrepancy could be more dependent on laboratory- than on patient-related factors.

Figure 1

Scatterplot of centrally measured factor activity with one-stage vs. chromogenic assay. The colored dots represent patients with assay discrepancy -red dots- or patients that did not meet these criteria but had an absolute difference >10 IU/dL between the assay results -yellow dots-. The line reflects x=y.

To cite this abstract in AMA style:

Zwagemaker A, Kloosterman F, Gouw S, Boyce S, Brons P, Cnossen M, Collins P, Eikenboom J, Hay C, Jackson S, Kruip M, Laros-van Gorkom B, Male C, Nieuwenhuizen L, Shapiro S, Fijnvandraat K, Coppens M. Little discrepancy of one-stage and chromogenic assays in a large international cohort of patients with non-severe hemophilia A and B (DYNAMO study) [abstract]. https://abstracts.isth.org/abstract/little-discrepancy-of-one-stage-and-chromogenic-assays-in-a-large-international-cohort-of-patients-with-non-severe-hemophilia-a-and-b-dynamo-study/. Accessed September 22, 2023.

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